Estrogen exposure and bladder cancer risk in Egyptian women

Abstract

Objective To examine associations between reproductive history and urinary bladder cancer in Egyptian women. Methods We used questionnaire data from an ongoing, multicenter case-control study in Egypt. Controls were matched on age and residence area. This analysis focused on female cases with confirmed urothelial (UC) and squamous cell (SCC) carcinoma of the bladder. Results We recruited 779 women (540 controls, 239 cases; >98.0% nonsmokers). Younger age at menopause (<45 y) and older age at first pregnancy (>18 y) were factors significantly associated with increased risk of bladder cancer, even after adjusting for schistosomiasis history and other covariates in the multivariable logistic model; adjusted odds ratio and 95% confidence intervals were 1.98 (1.41, 2.77) and 6.26 (3.46, 11.34), respectively. On the other hand, multiple pregnancies or use of oral contraceptives were associated with decreased odds of having bladder cancer. Similar associations were observed with UC and SCC when analyzed separately; however, the magnitude of association with SCC was lower than with UC. Conclusion Our data suggest that early estrogen exposure, or the relative lack of it, plays a role in urinary bladder carcinoma development among Egyptian women.

Chemoprevention of BBN-Induced Bladder Carcinogenesis by the Selective Estrogen Receptor Modulator Tamoxifen

“…Mice treated with tamoxifen either before (weeks 5-8) or after (weeks 20-32) BBN exposure were also significantly larger than control bladders by 2.5-fold and 1.5-fold, respectively (Wilcoxon Rank-Sum test, P < .0005). In contrast, the average bladder weights of groups 3 and 5 that received tamoxifen concurrent to (weeks [8][9][10][11][12][13][14][15][16][17][18][19][20] or during and after (weeks 8-32) BBN were not different from control animals; rather, they were significantly smaller than the bladder weights obtained for mice exposed to BBN alone (Wilcoxon Rank-Sum test, P < .0005). Body weights were recorded at the end of 32 weeks, but there were no statistically significant differences between the groups (data not shown).…”

“…Overall, the histopathologic results were consistent with the bladder weight data (Figure 2) in which the control group was significantly different from the groups tamoxifen treated pre-BBN (weeks 5-8) or post-BBN (weeks 20-32) as well as the BBN-alone group (Fisher exact test, P < .0001). Likewise, groups treated with tamoxifen concurrently with BBN (weeks [8][9][10][11][12][13][14][15][16][17][18][19][20] or during and after BBN (weeks 8-32) were significantly different from the BBN-only group (Fisher exact test, P < .0001) but not from the control group. Taken together, these results indicate that tamoxifen inhibits progression of tumorigenesis from non-muscle-invasive to muscle-invasive carcinoma regardless of when tamoxifen is administered.…”

“…With respect to non-muscle-invasive carcinoma, 55 μg/day tamoxifen administered concurrently with BBN (weeks [8][9][10][11][12][13][14][15][16][17][18][19][20] or during and after BBN exposure (weeks 8-32) yielded a very low level of disease, 14% and 7%, respectively, resulting in 86% and 90%, respectively, of the animals having bladders with normal histology (Figure 3). Thus, these treatment schedules were largely protective against BBN-induced bladder carcinogenesis.…”

“…For instance, women who experience early menopause are at higher risk [3], while parous women have a lower risk of bladder cancer than nulliparous women [10][11][12]. In addition, use of oral contraceptives and hormone replacement therapy also has been associated with reduced bladder cancer risk [13,14]. Further support for estrogens hindering urothelial carcinogenesis is found in adult rodent models of bladder cancer, for both males and females [15,16].…”

Can Reproductive Characteristics Predict Bladder Cancer in Women with Haematuria?

“…Wolpert et al (2010) claimed that delivering the first child after 18 years of age has been associated with reduced total amount of exposure to oestrogens in a life time and with an increased prevalence of bladder cancer. Cantor et al (1992) suggested that delivering the first child in later ages is associated with decreased risk of bladder cancer.…”